The effectiveness of idoxuridine in the treatment of herpes keratits infections of the stroma or inner eye structures is greatly reduced because of the poor permeation characteristics of the drug across the corneal membrane. The epithelial layer of the membrane being lipoidal in nature provides significant diffusional resistance to idoxuridine. For optimal results with the idoxuridine therapy, the infected tissues should be kept "saturated" with the drug. Presently, a "high frequency" dosing schedule is followed which requires the topical adminsitration of a 0.1% drug solution every hour during the day and every two hours during the night. It must be recognized that 99.9% to 99.99% of the instilled dose is drained out from the precorneal area through nasolacrimal drainage duct and undergoes systemic absorption. Therefore, apart from the patient compliance, large dose of administered drug might cause severe toxicity especially in light of the fact that idoxurdine has both oncogenic and mutagenic potential. The current proposal aims at developing novel 5' ester derivatives of idoxuridine which will be highly lipophilic and upon topical administration these compounds will be rapidly taken up by the lipoidal epithelium. The 5' esters will undergo corneal transport and simultaneous metabolism by the corneal epithelium as well as the stroma because these tissues contain a high quantity of nonspecific esterases. In-vitro corneal transport experiment with a series of homologous 5' esters or any combination of two will provide us with the information about the relationship between the optimum penetration characteristics and the physicochemical properties of the permeating species. This will substantially aid in the design of new prodrugs. In-vitro hydrolysis by isolated individual epithelial and stromal tissues will be evaluated and finally the sustained action and enhanced penetration rate of idoxuridine following the topical instillation of 5' ester prodrugs will be examined in-vivo in albino rabbits. The lowering of topical dose and a sustained drug action is urgently needed to improve the idoxuridine therapy.